The heart and coronary blood vessels receive constant sympathetic neural activity, referred to as tone, which modulates heart rate, contractile strength and coronary vascular resistance. Studies have indicated that there is a potential alteration in the sympathetic nervous system control, or the amount of sympathetic activity to the heart and blood vessels with exercise training. The proposed study was designed to investigate the relationship between the neural and metabolic regulation of coronary blood flow during an exercise training program. The hypothesis tested is: exercise training enhances the autonomic sympathetic tone on coronary vessels at rest and during physiological stress states, such as treadmill exercise. The sensitivity to adrenergic receptor agonists and antagonists will be studied in the chronically instrumented, conscious dog. Left circumflex coronary blood flow will be measured simultaneously with regional myocardial segment length using a range gated, pulsed Doppler flowmeter and ultrasonic dimension gages. Regional coronary blood flow distribution will be determined by the microsphere technique. Diastolic coronary vascular resistance will be calculated using diastolic aortic pressure and left circumflex coronary artery blood flow. Myocardial reactive hyperemia will be produced by occlusion and release of an externally controlled hydraulic occluder implanted around the circumflex coronary artery. Changes in coronary blood flow, diastolic coronary vascular resistance, myocardial segment length and heart rate to adrenergic stimulation of alpha- and beta-receptor agonists and to 15 sec coronary artery occlusions will be compared before, during and after a 10-week exercise training program. Drugs will be administered using an implanted coronary artery catheter, avoiding systemic drug effects. Using these techniques it is possible to perturb only the coronary vascular bed and measure both total and regional coronary blood flow in conscious dogs. We can also determine whether a modification in the sympathetic nervous system is real or if changes are metabolic in origin by simultaneously measuring regional myocardial function. The long term goal of these studies is to describe changes in the control of coronary blood flow due to daily exercise in normal individuals and to then apply this knowledge in the future to individuals with cardiovascular disease.